Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
  • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
  • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
  • C07D211/64—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having an aryl radical as the second substituent in position 4
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C253/00—Preparation of carboxylic acid nitriles
  • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups

Definitions

• European patent application EP 0 671 379 describes a process for the methylation of described organic compounds in the presence of trialkylamines and dimethyl carbonate. The The yield of ⁇ , ⁇ -dimethylbenzyl cyanide is 29%.
• U.S. Patent 3,668,255 describes a method of Alkylation of aliphatic ketones in the presence of tertiary amine and solid alkali bases described. Furthermore, the alkylation of benzyl cyanide with alkylating agents such as methyl iodide or Methyl chloride in the presence of strong bases such as sodium hydride, sodium amide or sodium alcoholate (Smith et al., J. Org. Chem.
• the object of the present invention is to find a method by which compounds of the formula II can be alkylated in high yields and purity.
• the procedure for the preparation of the compound of formula I is that the basic agent is used first and the compound of the formulas V and / or VI are introduced with stirring and then by addition the compound of formula II, optionally previously dissolved in an organic solvent was, and the alkylating agent is converted to a compound of formula I.
• the reaction temperature is from 20 ° C to 100 ° C, preferably from 30 ° C to 40 ° C.
• the reaction time is generally from 2 to 10 hours.
• the alkylating agent is gaseous, as is the case with methyl chloride (chloromethane), it can also be used with a Overpressure of up to 5 bar can be worked.
• the alkylation reaction with dialkyl sulfate methyl sulfuric acid formed during the reaction by optionally adding further Alkali hydroxide bound.
• the compound of the formula I is isolated the mixture is mixed with water and the resulting phases are then separated The compound of formula I is then obtained from the organic phase. If it appears necessary, the organic phase can be a cleaning process such as one Subject to distillation under reduced pressure or crystallization from a solvent become.
• Preferred alkali hydroxides are e.g. B. sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium hydroxide is particularly preferred.
• Preferred solvents are, for example: (C 5 -C 7 ) aliphatic and (C 6 -C 8 ) cycloaliphatic hydrocarbons such as pentane, 2-methylbutane, hexane, 2,2-dimethylbutane, 2-methylpentane, 3-methylpentane, heptane, cyclohexane, methylcyclohexane, 1 , 2-dimethylcyclohexane, 1,3-dimethylcyclohexane; aromatic hydrocarbons such as toluene, xylenes, ethylbenzene, isopropylbenzene; aromatic and aliphatic halogenated hydrocarbons such as chlorobenzene, dichloromethane, dichloropropane, 1,2-dichloroethane; Polyethers such as ethylene glycol dibutyl ether, diethylene glycol ethyl tert-butyl ether, polyethylene glycol dimethyl
• Preferred compounds of the formula V and / or VI are (C 3 -C 24 ) trioctylamine or (C 3 -C 24 ) trioctylphosphine.
• Particularly preferred compounds of the formula V and / or formula VI are trioctylamine, trioctylphosphine and triethylamine.
• Preferred alkylating agents are (C 1 -C 6 ) alkyl halides such as alkyl chloride, alkyl bromide, alkyl fluoride or alkyl iodide, in particular methyl chloride, ethyl chloride or propyl chloride; (C 1 -C 6 ) dialkyl sulfates such as dimethyl, diethyl, dipropyl, dibutyl, dipentyl or dihexyl sulfate or di (2-chloroethyl) methylamine.
• halogen means fluorine, chlorine, bromine or iodine.
• alkyl or "alkenyl” is understood to mean hydrocarbon radicals whose carbon chain is straight-chain or branched. Cyclic alkyl radicals are, for example, 3- to 6-membered monocycles such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. Furthermore, the alkenyl radical can contain more than one double bond, that is to say also 2, 3 or 4 double bonds.
• Preferred quaternary ammonium or phosphonium compounds of the formulas VII and VIII are Methyltrioctylammonium chloride, methyltrioctylammonium hydroxide, methyltricaprylammonium chloride, Methyl tricaprylammonium hydroxide, ethyl trioctylammonium chloride, ethyl trioctylphosphonium chloride and hexadecyltributylphosphonium bromide, especially methyltrioctylammonium chloride.
• the starting substances for the alkylation reaction according to the invention are known from the literature Process can be produced, for example by cyanolysis of the corresponding halogen compounds.
• the process products are sought compounds for the production of a variety of Derived products, e.g. for the production of antiallergic drugs such as 4- [4- [4- (hydroxydiphenyl) -1-piperidinyl] -1-hydroxybutyl] - ⁇ , ⁇ -dimethylphenylacetic acid (US 4,254,129).
• antiallergic drugs such as 4- [4- [4- (hydroxydiphenyl) -1-piperidinyl] -1-hydroxybutyl] - ⁇ , ⁇ -dimethylphenylacetic acid (US 4,254,129).
• the product was separated from the catalyst (trioctylamine, methyltrioctylammonium chloride) and organic impurities by initially acidic, then alkaline extraction.
• the toluene was then distilled off from the organic phase under reduced pressure.
• the distillation residue was then further purified by distillation under high vacuum at a pressure of less than 1 mbar.
• the distillate was 180 g of 1-methyl-4-phenyl-piperidine-4-carbonitrile with a content of more than 99% (determined by gas chromatography ( GC)). This corresponds to a yield of 90% of theory based on the benzyl cyanide used.
• GC separation column DB17, 30 m long Temp.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
• Hydrogenated Pyridines (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Applications Claiming Priority (4)

Publications (2)

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ID=26042529

Family Applications (1)

Country Status (23)

Families Citing this family (5)

Family Cites Families (8)

• 1998
  • 1998-12-09 AT AT98123418T patent/ATE243191T1/de active
  • 1998-12-09 PT PT98123418T patent/PT924196E/pt unknown
  • 1998-12-09 ES ES98123418T patent/ES2200260T3/es not_active Expired - Lifetime
  • 1998-12-09 DK DK98123418T patent/DK0924196T3/da active
  • 1998-12-09 EP EP98123418A patent/EP0924196B1/de not_active Expired - Lifetime
  • 1998-12-09 DE DE59808753T patent/DE59808753D1/de not_active Expired - Lifetime
  • 1998-12-15 NZ NZ333375A patent/NZ333375A/xx not_active IP Right Cessation
  • 1998-12-15 AR ARP980106374A patent/AR016435A1/es active IP Right Grant
  • 1998-12-15 HU HU9802909A patent/HU221417B1/hu unknown
  • 1998-12-15 CZ CZ19984148A patent/CZ293875B6/cs not_active IP Right Cessation
  • 1998-12-15 TR TR1998/02607A patent/TR199802607A3/tr unknown
  • 1998-12-15 UA UA98126635A patent/UA64711C2/uk unknown
  • 1998-12-15 ID IDP981630A patent/ID21458A/id unknown
  • 1998-12-16 NO NO19985895A patent/NO317334B1/no not_active IP Right Cessation
  • 1998-12-16 US US09/212,585 patent/US6143896A/en not_active Expired - Lifetime
  • 1998-12-16 AU AU97142/98A patent/AU740310B2/en not_active Expired
  • 1998-12-16 BR BRPI9805350-7A patent/BR9805350B1/pt not_active IP Right Cessation
  • 1998-12-16 CA CA002256941A patent/CA2256941C/en not_active Expired - Lifetime
  • 1998-12-17 PL PL330376A patent/PL194500B1/pl unknown
  • 1998-12-17 CN CN98125573A patent/CN1119322C/zh not_active Expired - Lifetime
  • 1998-12-17 JP JP35886898A patent/JP4410329B2/ja not_active Expired - Fee Related
  • 1998-12-17 KR KR1019980055570A patent/KR100589305B1/ko not_active IP Right Cessation
• 1999
  • 1999-12-03 HK HK99105667A patent/HK1020568A1/xx not_active IP Right Cessation
• 2009
  • 2009-09-17 JP JP2009215412A patent/JP4976472B2/ja not_active Expired - Lifetime

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